This phase I/II trial tests the safety and how well intravenous interferon-beta-1a (FP-1201) works in preventing toxicities after CD19-directed chimeric antigen receptor (CAR) T-cell therapy in patients with B-cell cancers that has come back after a period of improvement (recurrent) or that has not responded to previous treatment (refractory). Interferon beta-1a is in a class of medications called immunomodulators. It works by protecting the lining of blood vessels, and preventing brain inflammation. Giving FP-1201 may prevent cytokine release syndrome (CRS) and immune effector cell associated-neurotoxicity syndrome (ICANS) toxicities in patients receiving CD19 CAR T-cell therapy with recurrent or refractory B-cell malignancies.
Additional locations may be listed on ClinicalTrials.gov for NCT05936229.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To evaluate the safety and feasibility of treatment with FP-1201 in patients undergoing commercially available, Food & Drug Administration (FDA)-approved CD19 CAR T cell therapies axicabtagene ciloleucel (axi-cel) or brexucabtagene autoleucel (brexu-cel).
SECONDARY OBJECTIVES:
I. To decrease the incidence and severity of ICANS.
II. To decrease the incidence and severity of cytokine release syndrome (CRS).
III. To decrease corticosteroid usage.
IV. To evaluate the effect of FP-1201 on anti-tumor efficacy.
EXPLORATORY OBJECTIVES:
I. To characterize the in vivo response to FP-1201.
II. To evaluate the effects of FP-1201 on endothelial function.
III. To evaluate the effects of FP-1201 on the systemic cytokine milieu.
IV. To evaluate the effects of FP-1201 on in vivo CAR T-cell function in blood and in tumors.
V. Evaluate the presence of autoimmunity against type I interferons.
VI. To evaluate healthcare resource utilization.
OUTLINE: This is a dose-escalation study of FP-1201.
Patients undergo leukapheresis per standard of care (SOC) prior to treatment and receive FP-1201 intravenously (IV) for 3 days every 24 hours from day -3 through day -1 or for 5 days every 24 hours from day -5 through day -1 or on day -5, day -3, and day -1. Patients may receive lymphodepletion chemotherapy per SOC with either cyclophosphamide IV and fludarabine IV on days -5, -4, -3 followed by axi-cel IV or brexu-cel IV on day 0 or fludarabine IV over 30 minutes on days -4, -3, and -2 and cyclophosphamide IV over 60 minutes on day -2 followed by brexu-cel IV on day 0. Patients undergo x-ray imaging and echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients also undergo computed tomography (CT) or positron emission tomography (PET)/CT as well as lumbar puncture (LP) for cerebral spinal fluid (CSF) collection and/or bone marrow aspiration and biopsy as clinically indicated during screening and follow-up. Patients undergo blood sample collection on study and during follow-up as well as a tissue biopsy during screening and follow-up.
After completion of study treatment, patients are followed up to 28 days and 90 days, then long-term for up to 15 years.
Lead OrganizationFred Hutch/University of Washington/Seattle Children's Cancer Consortium
Principal InvestigatorJordan Gauthier
